Angiogenesis-modifying composition (A) containing at least one of a nucleic acid (I) from the gene encoding IRS-1 (insulin receptor substrate-1), or its complement or fragments, or a molecule (II) that inhibits expression of the nucleic acid, is new. ACTIVITY : Ophthalmological； Antiarthritic； Antirheumatic； Antiinflammatory； Gynecological； Antipsoriatic； Cytostatic； Vasotropic； Hypotensive； Vulnerary； Antianginal； Cardiant； Osteopathic. Corneal wounds were made in rats as described in Invest. Ophthalmol. Vis. Sci., 39 (1998) 18, then the animals given a subconjunctival injection of a composition containing 60 MicroM of the oligonucleotide (3), antisense to the IRS-1 gene 5'-TATCCGGAGGGCTCGCCATGCTGCT (3) in buffered saline, every day from days 4 to 9. The animals were killed on day 10 and the degree of neovascularization determined by staining with fluorescein-dextran, photography under a fluorescent microscope and then the ratio of neovascularized surface to total corneal surface was calculated. This ratio was 0.6157 (n = 15) for treated animals, compared with 0.9552 (n = 9) for those injected with saline only and 0.9170 (n = 9) for untreated animals, indicating a statistically significant reduction in neovascularization caused by (3). Similar results were obtained by topical application of an ointment containing 200 MicroM (3). MECHANISM OF ACTION : Antisense gene therapy.La présente invention a pour objet des compositions pharmaceutiques pour inhiber la formation de tubes capillaires par les cellules endothéliales, comprenant au moins un oligonucléotide capable d'inhiber l'expression de la protéine IRS-1. Les oligonucléotides selon l'invention sont indiqués comme agents anti-angiogéniques. Les compositions pharmaceutiques de l'invention sont particulièrement utiles pour le traitement de pathologies liées à l'angiogénèse.
